Thyroid Hormone Status Research Articles

Accustomed to the heat: Temperature and thyroid hormone influences on oogenesis and gonadal steroidogenesis pathways vary among populations of Amargosa pupfish (Cyprinodon nevadensis amargosae)

Many fish experience diminished reproductive performance under atypically high or prolonged elevations of temperature. Such high temperature inhibition of reproduction comes about in part from altered stimulation of gametogenesis by the hypothalamic-pituitary-gonadal (HPG) endocrine axis. Elevated temperatures have also been shown to affect thyroid hormone (TH) signaling, and altered TH status under high temperatures may impact gametogenesis via crosstalk with HPG axis pathways. Here, we examined effects of temperature and 3′-triiodo-L-thyronine (T3) on pathways for gonadal steroidogenesis and gametogenesis in Amargosa pupfish (Cyprinodon nevadensis amargosae) from two allopatric populations: 1) the Amargosa River – a highly variable temperature habitat, and 2) Tecopa Bore – an invariably warm groundwater-fed marsh. These populations were previously shown to differ in TH signaling profiles both in the wild and under common laboratory conditions. Sexually-mature pupfish from each population were maintained at 24 °C or 34 °C for 88 days, after which a subset of fish was treated with T3 for 18–24 h. In both populations, mRNA abundances for follicle-stimulating hormone receptor and luteinizing hormone receptor were higher in the ovary and testis at 24 °C compared to 34 °C. Females from Tecopa Bore – but not from the Amargosa River – also had greater ovarian transcript abundances for steroidogenic enzymes cytochrome P450 aromatase, 3β-hydroxysteroid dehydrogenase, and 17β-hydroxysteroid dehydrogenase at 24 °C compared to 34 °C, as well as higher liver mRNA levels of vitellogenins and choriogenins at cooler temperature. Transcript abundances for estrogen receptors esr1, esr2a, and esr2b were reduced at 34 °C in Amargosa River females, but not in Tecopa Bore females. T3 augmented gonadal gene transcript levels for steroid acute regulatory protein (StAR) transporter in both sexes and populations. T3 also downregulated liver estrogen receptor mRNAs in females from the warmer Tecopa Bore habitat only, suggesting T3 modulation of liver E2 sensitivity as a possible mechanism whereby temperature-induced changes in TH status may contribute to shifts in thermal sensitivity for oogenesis.

Is TSH a Reliable Indicator of Thyroid Hormone Status in Pregnancy?

Thyroid screening is recommended during pregnancy with serum thyrotropin (TSH) as the primary test. However, since human chorionic gonadotropin, the serum hallmark of pregnancy, has TSH-like effects, the adequacy of TSH as a screening tool in this constellation requires further study. This study aimed to evaluate the relationship between TSH and thyroid hormones during pregnancy in order to determine if TSH is an adequate screening tool. This was a retrospective study utilizing the Clalit Health Service, Jerusalem district database between 2006-2017 in which we analyzed TSH, FT4 and FT3 measurements from 32430 pregnancies resulting in live birth. We grouped FT4 and FT3 levels by trimester and by the following TSH levels: (1) below 0.1/0.2/0.3 mIU/l, (2) 0.1-2.5/0.2-3.0/0.3-3.0 mIU/l, (3) 2.6-4.0/3.1-4.0 mIU/l, (4) 4.1-10.0 mIU/l and (5) above 10.0 mIU/l. In the first trimester, the most important for fetal brain development, FT3 was below normal, defined as below the 2.5th percentile for the population, in only 15.3% of tests with TSH over 10 mIU/l. FT4 was below normal in only 12.8% of such tests. Similar findings were noted for the second and third trimesters. As expected, there were far less abnormal tests when lower TSH cutoff levels were tested. In conclusion, TSH levels beyond the range accepted as normal do not, in most cases, reflect abnormal thyroid hormone levels during pregnancy. TSH is not a good screen for overt hypothyroidism in pregnancy. This may be due, at least in the first trimester, to thyrotropic effects of HCG.

Assessment of Joint Impact of Iodine, Selenium, and Zinc Status on Women's Third-Trimester Plasma Thyroid Hormone Concentrations

ABSTRACTBackgroundIodine is essential for synthesizing thyroid hormones, but other micronutrients are also required for optimal thyroid function. However, there is a lack of data on combined micronutrient status in relation to thyroid hormones in pregnancy.ObjectivesWe aimed to assess the joint associations of iodine, selenium, and zinc status with plasma concentrations of thyroid hormones and thyroid-stimulating hormone (TSH) in pregnancy.MethodsWe included 531 pregnant women (aged 22–40 y) participating in a Swedish birth cohort who provided blood and spot urine samples in gestational weeks 27–33 (mean: 29). Associations of urinary iodine concentration (UIC), plasma selenium concentration, and plasma zinc concentration (measured by inductively coupled plasma mass spectrometry) with plasma hormone concentrations [total and free thyroxine (tT4, fT4), total and free triiodothyronine (tT3, fT3), and TSH] were explored with Bayesian kernel machine regression (BKMR; n = 516; outliers excluded) and multivariable-adjusted linear regression (n = 531; splined for nonlinear associations).ResultsMedian (IQR) micronutrient concentrations were 112 μg/L (80–156 μg/L) for UIC, 67 μg/L (58–76 μg/L) for plasma selenium, and 973 μg/L (842–1127 μg/L) for plasma zinc; the former 2 median values were below recommended concentrations (150 μg/L and 70 μg/L, respectively). Mean ± SD TSH concentration was 1.7 ± 0.87 mIU/L, with 98% < 4 mIU/L. BKMR showed a positive trend of joint micronutrient concentrations in relation to TSH. Plasma zinc was most influential for all hormones but tT3, for which plasma selenium was most influential. In adjusted linear regression models, zinc was positively associated with tT4, tT3, and TSH, and <1200 μg/L also with fT4 and fT3. Selenium was inversely associated with fT3, and <85 μg/L with tT3.ConclusionsPregnant women's plasma TSH concentrations in the early third trimester increased with increasing joint status of iodine, selenium, and zinc. Zinc and selenium were more influential than iodine for the hormone concentrations. Multiple micronutrients need consideration in future studies of thyroid hormone status.

3,5-T2-an Endogenous Thyroid Hormone Metabolite as Promising Lead Substance in Anti-Steatotic Drug Development?

Thyroid hormones, their metabolites, and synthetic analogues are potential anti-steatotic drug candidates considering that subclinical and manifest hypothyroidism is associated with hepatic lipid accumulation, non-alcoholic fatty liver disease, and its pandemic sequelae. Thyromimetically active compounds stimulate hepatic lipogenesis, fatty acid beta-oxidation, cholesterol metabolism, and metabolic pathways of glucose homeostasis. Many of these effects are mediated by T3 receptor β1-dependent modulation of transcription. However, rapid non-canonical mitochondrial effects have also been reported, especially for the metabolite 3,5-diiodothyronine (3,5-T2), which does not elicit the full spectrum of “thyromimetic” actions inherent to T3. Most preclinical studies in rodent models of obesity and first human clinical trials are promising with respect to the antisteatotic hepatic effects, but potent agents exhibit unwanted thyromimetic effects on the heart and/or suppress feedback regulation of the hypothalamus-pituitary-thyroid-periphery axis and the fine-tuned thyroid hormone system. This narrative review focuses on 3,5-T2 effects on hepatic lipid and glucose metabolism and (non-)canonical mechanisms of action including its mitochondrial targets. Various high fat diet animal models with distinct thyroid hormone status indicate species- and dose-dependent efficiency of 3,5-T2 and its synthetic analogue TRC150094. No convincing evidence has been presented for their clinical use in the prevention or treatment of obesity and related metabolic conditions.

The Clinical Relevance of Hypothyroidism in Patients with Solid Non-Thyroid Cancer: A Tantalizing Conundrum.

Hypothyroidism in patients with solid non-thyroid cancer is a tantalizing entity, integrating an intriguing thyroid hormones (THs)–cancer association with the complexity of hypothyroidism itself. The present narrative review provides a comprehensive overview of the clinical relevance of hypothyroidism in solid non-thyroid cancer. Hypothyroidism in patients with solid non-thyroid cancer is reminiscent of hypothyroidism in the general population, yet also poses distinct challenges due to the dual role of THs in cancer: promoting versus inhibitory. Close collaboration between oncologists and endocrinologists will enable the prompt and personalized diagnosis and treatment of hypothyroidism in patients with solid non-thyroid cancer. Clinical data indicate that hypothyroidism is a predictor of a decreased or increased risk of solid non-thyroid cancer and is a prognostic factor of favorable or unfavorable prognosis in solid non-thyroid cancer. However, the impact of hypothyroidism with respect to the risk and/or prognosis of solid non-thyroid cancer is not a consistent finding. To harness hypothyroidism, or THs replacement, as a personalized anticancer strategy for solid non-thyroid cancer, four prerequisites need to be fulfilled, namely: (i) deciphering the dual THs actions in cancer; (ii) identifying interventions in THs status and developing agents that block tumor-promoting THs actions and/or mimic anticancer THs actions; (iii) appropriate patient selection; and (iv) counteracting current methodological limitations.

Comparison of thyroid hormonal status and serum albumin level between children with moderate acute malnutrition and severe acute malnutrition

Background: Malnutrition is one of the most common nutritional problems in developing countries of the world and an important cause of childhood mortality and morbidity leading to permanent impairment of physical and mental growth. Objective of current study was comparison of thyroid hormonal status and serum albumin level between children with MAM and SAM. Methods: The present study was a hospital-based Descriptive comparative study. A total of 96 children aged 6 months to 5 years were enrolled. They were divided into two groups (MAM and SAM) based on WHO staging for malnutrition. A detailed clinical examination was done. Thyroid function test and Serum albumin were done. Statistical analysis was performed.Results: Children with SAM have low levels of albumin, T3, T4, FT4 as compared to children with MAM. The difference was statistically significant (p value &lt;0.01). The Serum TSH levels were comparable among two groups. Significant positive correlation between mean T3 and T4 levels of children with MAM with serum albumin was observed and significant positive correlation of T3, T4, and FT4 was observed in SAM. Serum TSH level in both categories does not correlate with serum albumin.Conclusions: Children with MAM and SAM have low albumin levels probably due to decreased intake of proteins and reduced biosynthesis. Serum T3, T4 and FT4 levels are lower in children with MAM and SAM probably due to reduction in circulating plasma proteins.

Higher free thyroxine associated with PFAS exposure in first trimester. The Odense Child Cohort.

BackgroundPerfluoroalkyl substances (PFAS) are endocrine disrupting chemicals with elimination half-lives ranging from four to eight years. Experimental studies found PFAS able to interfere with thyroid hormone-binding proteins. During the first 20 weeks of gestation (GW), the fetus is reliant on placental transfer of maternal thyroid hormones, mainly free thyroxine (FT4). However, previous studies investigating associations between exposure to PFAS and thyroid hormone status mainly focused on blood samples from late pregnancy or umbilical cord with mixed findings. ObjectivesTo investigate associations between serum-PFAS concentrations and thyroid hormone status in early pregnancy as reflected by FT4 and thyroid-stimulating hormone (TSH). MethodsIn the Odense Child Cohort, a single-center study, we measured maternal pregnancy serum concentrations of five PFAS: perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA); and FT4 and TSH in 1048 pregnant women at median GW 12 (25th, 75th percentile: 10, 15). Multivariate linear regression models were performed to estimate associations between PFAS exposure and thyroid hormone status. ResultsA doubling in PFOS, PFOA, and PFNA concentrations was associated with an increment in FT4 concentration by 1.85% (95% CI: 0.66%, 3.05%), 1.29% (95% CI: 0.21%, 2.39%), and 1.70% (95% CI: 0.48%, 2.94%), respectively, in adjusted analyses. A statistically significant dose-response relationship was observed across exposure quartiles for PFOS, PFOA, and PFNA in the association with FT4. No association was found between concentrations of PFAS and TSH in adjusted analyses. ConclusionExposure to PFOS, PFOA, and PFNA was associated with higher FT4 concentrations in women during early pregnancy. The potential clinical implications of these findings remain to be clarified.

Associations of exposure to metal and metal mixtures with thyroid hormones: Results from the NHANES 2007–2012

BackgroundDisrupted thyroid homeostasis plays a role in neurocognitive dysfunction and metabolic disorders. Since individuals are exposed to multiple metals simultaneously, it is important to assess the effects of metal mixtures on thyroid hormone status. This study aimed to investigate the associations of metal mixtures and individual metals with thyroid hormone levels. MethodsData included 2399 men and 1988 women from the 2007–2012 National Health and Nutrition Examination Survey (2007–2012). Thyroid hormones measured included total triiodothyronine (T3), total thyroxine (T4), free forms of T3 (FT3) and T4 (FT4), and thyroid stimulating hormone (TSH). We included twelve metals (arsenic, barium, cobalt, cesium, molybdenum, antimony, thallium, tungsten, and uranium from urine; cadmium, lead, and mercury from blood) in traditional linear regression models controlling for 12 metals simultaneously and in quantile-based g-computation (QGC) to assess the relative contribution of each metal as well as the overall association with thyroid hormones as a metal mixture. ResultsThere were associations of the total metal mixture with thyroid hormones for T3 (beta: −0.023, 95% CI: −0.04, −0.01, in women), T4 (beta: −0.03, 95% CI: −0.05, −0.01, in men; beta: −0.026, 95% CI: −0.04, −0.01, in women), and the T3:T4 ratio (beta: 0.026, 95% CI: 0.01, 0.05, in men). Arsenic had negative contributions to T3 and T4. Cadmium had a positive contribution to T4 but negative contributions to T3 and T3:T4. Lead had a positive contribution to T3 and T3:T4, but a negative contribution to T4. ConclusionMultiple metals as a mixture were associated with thyroid hormone levels. Arsenic, cadmium, and lead were individually associated with multiple thyroid hormones. Examination of associations of metal mixtures and individual metals with thyroid hormones can contribute to an understanding of thyroid hormone homeostasis and provide evidence for developing intervention and guidance for health promotion.

Biomarkers indicating tissue thyroid hormone status: ready to be implemented yet?

Currently, thyroid hormone status is predominantly determined by the measurement of serum thyroid-stimulating hormone and free thyroxine. Although it is assumed that serum thyroid hormone (TH) concentrations within the reference range represent euthyroidism, it is unknown whether this reflects euthyroidism in all tissues (e.g. brain, muscle, bone and liver). To date, no serum marker has been established for clinical use that represents TH status within tissues accurately. However, several biomarkers have been investigated and innovative techniques have been used to unravel new biomarkers. This review provides an overview of proposed serum biomarkers that reflect tissue TH status in humans. Furthermore, we discuss the feasibility of these serum markers in clinical practice.

Nano-selenium supplementation in plant protein-based diets changed thyroid hormones status and hepatic enzymes activity in Acanthopagrus arabicus female broodfish and their offspring

A feeding trial was conducted to assess the effects of nano-selenium (n.Se) supplementation in a plant protein (PP)-based diet on female Acanthopagrus arabicus broodfish and their offspring. Two basal diets were prepared: a fish meal (FM)-based diet (FM-control) as a positive control and a PP-based diet. The PP-based diet was supplemented with n.Se at five levels including 0 (PP-control, as a negative control), 0.5, 1, 2, and 4 mg/ Kg. Brooders were fed for 90 days with one of the six experimental diets. Supplementing the PP-based diet with 2–4 mg n.Se/Kg markedly enhanced survival rate in 3-day post-hatch larvae (3DPH) larvae and total body length in newly born and 3DPH larvae. Serum triiodothyronine (T3) significantly decreased in females by supplementing PP-based diet with 1–4 mg n.Se/kg, meanwhile, serum thyroxine (T4) increased in females fed 1–4 mg n.Se/kg PP-based diets. The level of serum T3 in females fed FM-based diet was lower than those fed PP-based diet without n.Se supplementation (0.6 vs. 1.9 nmol/L−1). Meanwhile, the serum T4 was markedly higher in broodfish fed the FM-based diet than those fed the PP-based diet (21.9 vs. 14.3 nmol/L−1). The levels of T3 and T4 in 3DPH larvae originating from females fed the PP-based diet without n.Se supplementation were lower than in FM-based and n.Se supplemented PP-based groups (P < 0.05). Serum alkaline phosphatase (ALP) increased in females with increasing n.Se level in the PP-based diet. The highest and lowest ALP levels were in 3DPH larvae originating from females fed PP-based diet without n.Se supplementation and those fed with 1 mg n.Se/Kg PP-based diet, respectively (P < 0.05). The results of the present study suggest supplementing 2–4 mg n.Se in a PP-based diet can improve performance in A. arabicus brooders and larvae that are associated with modulation of thyroid hormones in this species.

An animal model for Pierpont syndrome: a mouse bearing the Tbl1xr1Y446C/Y446C mutation.

Pierpont syndrome is a rare disorder characterized mainly by global developmental delay, unusual facial features, altered fat distribution in the limbs and hearing loss. A specific mutation (p.Tyr446Cys) in TBL1XR1, encoding a WD40 repeat-containing protein, which is a component of the SMRT/NCoR (silencing mediator retinoid and thyroid hormone receptors/nuclear receptor corepressors), has been reported as the genetic cause of Pierpont syndrome. Here, we used CRISPR-cas9 technology to generate a mutant mouse with the Y446C mutation in Tbl1xr1, which is also present in Pierpont syndrome. Several aspects of the phenotype were studied in the mutant mice: growth, body composition, hearing, motor behavior, thyroid hormone state and lipid and glucose metabolism. The mutant mice (Tbl1xr1Y446C/Y446C) displayed delayed growth, altered body composition with increased relative lean mass and impaired hearing. Expression of several genes involved in fatty acid metabolism differed in white adipose tissue, but not in liver or muscle of mutant mice compared to wild-type mice (Tbl1xr1+/+). No difference in thyroid hormone plasma concentrations was observed. Tbl1xr1Y446C/Y446C mice can be used as a model for distinct features of Pierpont syndrome, which will enable future studies on the pathogenic mechanisms underlying the various phenotypic characteristics.

Does drinking water with raised fluoride content affect the thyroid hormone status: A study from Tharparker Pakistan.

To determine the effect of consuming water with high fluoride content on thyroid hormone status. The comparative cross-sectional study was conducted at Sammu Rind village of district Tharparkar, Pakistan, where ground water was the only source of drinking and had fluoride content >6-8mg/dL, and another set of people from Gadap Town, Karachi, where ground water had fluoride level of 0.3mg/L. Thyroid profile, including serum thyroid stimulating hormone, free triiodothyronine and free thyroxine, were checked for both the exposed and the unexposed groups, and data was cross-tabulated with thyroid profile to check statistical significance. Data was analysed using SPSS 20. Of the 242 subjects, 121(50%) each were in the exposed and the unexposed group. Among the exposed, 15(12.4%) people had hypothyroidism, 104(86%) had euthyroid and 2(1.6%) had hyperthyroid. Corresponding values in the unexposed group were 10(8%), 105(87%) and 6(5%). The difference was not statistically significant (p>0.05).

Interplay Between Thyroid Hormone Status and Pulmonary Hypertension in Graves' Disease: Relevance of the Assessment in Thyrotoxic and Euthyroid Patients.

BackgroundGraves’ disease (GD) is the most common cause of hyperthyroidism and can cause cardiac changes, such as pulmonary hypertension.MethodsThis is a prospective study in which we obtained demographic, clinical, laboratory data and characteristics of the GD, in addition to investigating cardiorespiratory function, focusing on the detection of pulmonary hypertension. Patients were separated into two groups: thyrotoxicosis and euthyroidism. Ninety patients with GD of both sexes, over 18 years of age, were included. The cardiorespiratory assessment included an echocardiographic evaluation, a questionnaire of specific symptoms, spirometry and a six-minute walk test.ResultsThe hyperthyroid group included 42 patients (47.73%) and the euthyroid group 46 patients (52.27%); 78 were women (86.67%). The prevalence of pulmonary hypertension between the hyperthyroidism (48.57%) and the euthyroidism (29.41%) groups was not different. Free thyroxine levels (FT4) (OR 1.266), higher left atrium volume (OR 1.113) and right ventricle diameter were associated with pulmonary hypertension. A direct correlation between FT4 with forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), as also an inverse correlation between initial oxygen saturation (SpO2) with diagnostic time and drop SpO2 with the ratio between the diastolic velocity E of the mitral flow and the diastolic velocity of the mitral ring (E/e’) were observed in the euthyroid group. An inverse correlation between FT4 levels with walked distance as % of predicted value, and a direct correlation between E/e’ ratio and walked distance as % of predicted value were observed in the hyperthyroid group.ConclusionWe emphasize the importance of a cardiorespiratory reassessment in GD, even after a long-term control of the thyrotoxic state, as we demonstrate that about 30% of these patients remain with PH and are subject to specific treatment.

Thyroid hormone status during pregnancy in Bangladesh

Thyroid hormone status during pregnancy in Bangladesh

Role of thyroid hormone in an experimental model of atherosclerosis: the potential mediating role of immune response and autophagy.

Accumulating evidence has revealed that several conditions related to abnormal thyroid hormone status, such as dyslipidemia, hypertension, or hypercoagulable state, can exacerbate atherosclerotic vascular disease. Thyroid hormone effects on vascular smooth muscle cells and endothelial cells have also been studied extensively. However, only limited information is available on thyroid hormone-mediated immune response in current review articles on the pathophysiology of atherosclerosis. This report thus presents an overview of the recent advances in the understanding of the dynamic interactions taking place between thyroid hormone status and immune response in the pathogenesis of atherosclerosis. In particular, we focus on macrophages and T-lymphocytes, which have been recognized as important determinants for the initiation and development of atherosclerosis. Numerous studies have revealed the role of autophagy in immune cells produced in atherosclerosis. In addition, thyroid hormones induce autophagy in several cells and tissues, such as liver, skeletal muscles, lungs, and brown adipose tissue. Our research group, among others, have reported different targets of thyroid hormone-mediated autophagy, including lipid droplets (lipophagy), mitochondria (mitophagy), and aggregated proteins (aggrephagy). Based on these findings, thyroid hormone-mediated autophagy could serve as a novel therapeutic approach for atherosclerosis. We also consider the limitations of the current murine models for studies on atherosclerosis, especially in relation to low-density lipoprotein-cholesterol driven atherosclerotic plaque.

Spectrum of thyroid function test among type 2 diabetic patients attending a rural health facility, southwest Nigeria: A hospital-based study.

Objectives:The thyroid gland produces hormones that have significant influence on carbohydrate metabolism; its disorders may affect carbohydrate metabolism in type 2 diabetic patients (T2DM) more than the non-diabetic (NDM) patients as reported in various studies. We determined the spectrum of thyroid function tests (TFTs) profile among T2DM in our rural health facility.Methods:T2DM patients and NDM patients were recruited for the study. The age, educational level, occupation, marital status, and duration of diabetes were extracted from interviewer’s administered questionnaire. The weight, height, body mass indices (BMIs), and the waist and hip circumferences were measured. Waist-hip ratios (WHR) were calculated for all participants. Venous blood was collected and assayed for free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) using a Chemiluminescence Immunoassay (CLIA) 2nd Generation Autoanalyzer. The mean, standard deviation, frequencies, and percentages were calculated for the variables. The student’s t-test and chi-square test were also determined as appropriate.Results:Seventy-eight patients made up of 56 T2DM and 22 NDM were evaluated in this study. Fifty-one were males while 27 were females; 67.9% and 59.1% of the female participants were T2DM and NDM, respectively. The WHR was significantly higher in T2DM than NDM (0.92 ± 0.05 versus 0.88 ± 0.06). The TSH was higher in T2DM than the NDM. Forty-four (78.6%) of the T2DM had euthyroid (normal) biochemical pattern; 12 (21.4%) showed abnormal biochemical pattern of euthyroid sick syndrome, subclinical hyperthyroid, and subclinical hypothyroid. Thirty (53.6%) of the T2DM were diagnosed less than five years ago. The value of TSH was increasing with the duration of diabetes but not in a statistically significant way. None of the T2DM showed overt hypothyroid or hyperthyroid test result.Conclusion:Thyroid function test may identify diabetics with altered thyroid hormone status that may impact on their metabolic control. Knowledge of the functional state of the thyroid gland can help in achieving a better metabolic control and attenuate the development of complications in T2DM.

Screening for Hypothyroidism in children with severe acute malnutrition at Nutrition Rehabilitation Center, Children’s Hospital and Institute of Child Health Multan.

Objective: To determine the percentage of Hypothyroidism in children with severe acute malnutrition. Study Design: Cross Sectional study. Setting: Nutrition Rehabilitation Center, Children’s Hospital and Institute of Child Health Multan. Period: January 2019 to December 2019. Material &amp; Methods: A total of 255 malnourished patients (as per inclusion criteria) were included in current study. A written Performa was designed to collect history, anthropometric measurements and systemic examination. Taking aseptic measures venous blood was sent for baseline tests as well as for T3, T4 and TSH, total serum protein albumin and total ferritin levels to hospital laboratory. Correlation between serum thyroid concentrations and total protein, albumin, hemoglobin and serum ferritin were estimated by using t-test and p-vlaue less than 0.05 was considered as significant. Total collected data was entered and analyzed in SPSS version 21.0. Results: A total of 255 malnourished children were included in this study. Majority of studied subjects were male (52.5%) with 83.92%, 3-5 years of age. Amongst the 255 children mean values of T3 in MAM and SAM patients were 105.4 ng/dl and 89.7 ng/dl respectively. There was a statistically significant (p &lt;0.001) association between decreased T3 and type of malnutrition. Similarly, mean values of T4 in MAM and SAM patients were 6.3 ug/dl and 5.7 ug/dl respectively that was statistically significant (p &lt;0.05). Lower values of T4 were higher among SAM children in 1 to 3 years age group compared to respective MAM children with p value .0.05 and high T4 value in 3-5 years age group of MAM children were both statistically insignificant. Higher mean Values of TSH was found in SAM compared to MAM children both age groups. Conclusion: Severe acute malnutrition (SAM) is associated with reduction in T3 and T4 levels and higher levels of TSH in SAM children as compared to MAM. The altered thyroid hormone status in children with PEM is perhaps a protective phenomenon to limit protein catabolism and lower energy requirements.

Iodine intake and neonatal thyroid function: A never-ending story

Iodine deficiency in pregnant women can lead to abortion, dysgravidy, intrauterine growth restriction, premature birth, low birth weight, which places the pregnant woman in a group with increased vulnerability to the lack of adequate amounts of iodine. Iodine deficiency in pregnancy can lead to increased perinatal and infant mortality and the prevalence of congenital anomalies. All these aspects shed new light on the many side effects of iodine deficiency during pregnancy. The present paper aligns with the general trend of assessing the maternal-fetal thyroid hormone status and establishing the most accurate indicators for its quantification and taking into account the degree of iodine deficiency and prematurity.

Cord Blood Thyroid Hormones and Neurodevelopment in 2-Year-Old Boys and Girls.

Objective: Thyroid hormones are essential for neurodevelopment in early life. However, the impact of mild alterations in neonatal thyroid hormones on infant neurodevelopment and its sex dimorphism is unclear. We aimed to assess whether mild variations in neonatal thyroid hormones of term-born newborns with maternal euthyroid are related to neurodevelopment in 2-year-old boys and girls.Methods: This study used data from 452 singleton term-born infants of mothers with normal thyroid function in Shanghai, China, and their follow-up measure at the age of 2 years. Cord serum concentrations of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured by chemiluminescent microparticle immunoassays and classified into three groups: the low (1st, Q1), middle (2nd−4th, Q2–Q4), and high (5th, Q5) quintiles. Neurodevelopment indices were assessed using the Ages and Stages Questionnaire, third edition (ASQ-3), at 24 months of age.Results: Compared to infants with thyroid hormones in the middle (Q2–Q4), boys with FT4 in the lowest quintile had 5.08 (95% CI: 1.37, 8.78) points lower scores in the communication domain, 3.25 (0.25,6.25) points lower scores in the fine motor domain, and 3.84 (0.04, 7.64) points lower scores in the personal-social domain, respectively. Boys with FT3 in the highest quintile had 4.46 (0.81, 8.11) points increase in the personal-social domain. These associations were not observed in girls. No associations were observed between cord blood serum TSH and ASQ-assessed neurodevelopment in the boys or the girls.Conclusions: Mild alterations in thyroid hormones of newborns were associated adversely with neurodevelopment in boys, suggesting the importance of optimal thyroid hormone status for neurodevelopment in early life.

Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase.

Besides their direct effects on peripheral metabolic tissues, thyroid hormones (TH) act on the hypothalamus to modulate energy homeostasis. However, since most of the hypothalamic actions of TH have been addressed in studies with direct central administration, the estimation of the relative contribution of the central vs. peripheral effects in physiologic conditions of peripheral release (or administration) of TH remains unclear. In this study we used two different models of peripherally induced hyperthyroidism (i.e., T4 and T3 oral administration) to assess and compare the serum and hypothalamic TH status and relate them to the metabolic effects of the treatment. Peripheral TH treatment affected feeding behavior, overall growth, core body temperature, body composition, brown adipose tissue (BAT) morphology and uncoupling protein 1 (UCP1) levels and metabolic activity, white adipose tissue (WAT) browning and liver metabolism. This resulted in an increased overall uncoupling capacity and a shift of the lipid metabolism from WAT accumulation to BAT fueling. Both peripheral treatment protocols induced significant changes in TH concentrations within the hypothalamus, with T3 eliciting a downregulation of hypothalamic AMP-activated protein kinase (AMPK), supporting the existence of a central action of peripheral TH. Altogether, these data suggest that peripherally administered TH modulate energy balance by various mechanisms; they also provide a unifying vision of the centrally mediated and the direct local metabolic effect of TH in the context of hyperthyroidism.